MicroRNAs (miRNAs) are endogenous small non-coding single stranded RNAs that control diverse biological processes and major signaling pathways, like developmental timing, hematopoietic cell differentiation, apoptosis, cell proliferation, and organ development. They regulate the expression of complementary target mRNAs by post-transcriptional gene silencing, which leads to mRNA cleavage or translational repression. With more than 200 members per species in higher eukaryotes, miRNAs are one of the largest gene families accounting for about 1% of the genome (Bartel, 2004). More than one third of all human genes are targeted by miRNAs. MiRNAs and their targets seem to form complex regulatory networks. For example, a single miRNA regulates many different mRNA targets, and several different miRNAs control a single mRNA target. Consequently, the unique combination of miRNAs that are expressed in each cell type might affect the utilization of thousands of mRNAs.
MiRNAs were recently implicated in the regulation of diverse cardiac functions in a series of genetic studies (Care et al., 2007). Myocardial infarction results in hypoxia of cardiac tissue that triggers an array of pathophysiological effects including cardiomyocyte apoptosis and impairment of vascularization. Studies have shown miRNAs to be important for regulation of endothelial function, especially angiogenesis (Wang et al., 2008). Although these studies help to delineate the role of miRNA in heart physiology, growth and morphogenesis, molecular mechanisms for miRNAs in cardiac disease pathways are poorly understood. MiR-24 is expressed in a variety of organs (FIG. 6), but its role in the cardiovascular system is unclear. Therefore, the therapeutic potential of specific miRNAs and their antagonists in cardiac diseases remains to be established.
Myocardial infarction and cardiac dysfunction represent a critical health burden worldwide (http://www.who.int/whosis/whostat/2009/en/index.html, WHO, 2009). Due to the increased life expectancy, incidence and prevalence of cardiovascular diseases will rise. Cardiac ischemia triggers left ventricular remodeling and development of heart failure, and the prognosis of heart failure is as bad as for certain malignant tumors (Hill et al., 2008). A central issue of ventricular remodeling after myocardial infarction is an insufficient angiogenesis. Therapies improving neovascularization after myocardial infarction favorably affect cardiac outcome, however, such approaches are scarce and mechanistically not well understood.
Therefore, therapies for the improvement in particular of cardiac healing processes post cardiovascular diseases have to be developed.
The solution to this problem is achieved by providing the embodiments characterized by the claims, and described further below.